tbuckley/cabot-search huggingface dataset:
Exercise-induced release of cardiac and skeletal muscle injury biomarkers in patients with chronic myeloid leukemia receiving TKI therapy
Authors: Lando Janssen, Neeltje A. E. Allard, Vincent L. Aengevaeren, Thijs M. H. Eijsvogels, Silvie Timmers, Nicole M. A. Blijlevens, Maria T. E. Hopman
Journal: Blood Cancer Journal (2023)

Exercise-induced
Mitochondrial pyruvate metabolism and glutaminolysis toggle steady-state and emergency myelopoiesis
Authors: Hannah A. Pizzato, Yahui Wang, Michael J. Wolfgang, Brian N. Finck, Gary J. Patti, Deepta Bhattacharya
Journal: The Journal of Experimental Medicine (2023)

To define the metabolic requirements of hematopoiesis, we examined blood lineages in mice conditionally deficient in genes required for long-chain fatty acid oxidation (Cpt2), glutaminolysis (Gls), or mitochondrial pyruvate import (Mpc2). Genetic ablation of Cpt2 or Gls minimally impacted most blood lineages. In contrast, deletion of Mpc2 led to a sharp decline in mature myeloid cells and a slower reduction in T cells, whereas other hematopoietic lineages were unaffected. Yet MPC2-deficient monocytes and neutrophils rapidly recovered due to a transient and specific increase in myeloid progenitor proliferation. Competitive bone marrow chimera and stable isotope tracing experiments demonstrated that this proliferative burst was progenitor intrinsic and accompanied by a metabolic switch to glutaminolysis. Myeloid recovery after loss of MPC2 or cyclophosphamide treatment was delayed in the absence of GLS. Reciprocally, MPC2 was not required for myeloid recovery after cyclophosphamide treatment. Thus, mitochondrial pyruvate metabolism maintains myelopoiesis under steady-state conditions, while glutaminolysis in progenitors promotes emergency myelopoiesis.
Is COVID-19 Care Better in Veterans Health Administration Hospitals,<i>Ceteris Paribus</i>?
Authors: Michael Klompas, Barbara E. Jones
Journal: JAMA Network Open (2023)

Michael E. Ohl, MD, MSPH; Kelly Richardson Miell, PhD; Brice F. Beck, MA; Bradley Mecham, PhD; George Bailey, MS; Michelle Mengeling, PhD; Mary Vaughan-Sarrazin, PhD
Précis of <i>What Babies Know</i>
Authors: Elizabeth S. Spelke
Journal: Behavioral and Brain Sciences (2023)

Abstract Where does human knowledge begin? Research on human infants, children, adults, and nonhuman animals, using diverse methods from the cognitive, brain, and computational sciences, provides evidence for six early emerging, domain-specific systems of core knowledge. These automatic, unconscious systems are situated between perceptual systems and systems of explicit concepts and beliefs. They emerge early in infancy, guide children's learning, and function throughout life.
Elevated Mast Cell Abundance Is Associated with Enrichment of CCR2+ Cytotoxic T Cells and Favorable Prognosis in Lung Adenocarcinoma
Authors: Fanfan Fan, Jian Gao, Yue Zhao, Jun Wang, Lu Meng, Jiaqiang Ma, Teng Li, Han Han, Jinglei Lai, Zhendong Gao, Xiongfei Li, Ran Guo, Zhiwei Cao, Yang Zhang, Xiaoming Zhang, Haiquan Chen
Journal: Cancer Research (2023)

Abstract Mast cells constitute indispensable immunoregulatory sentinel cells in the tumor microenvironment. A better understanding of the regulation and functions of mast cells in lung adenocarcinoma (LUAD) could uncover therapeutic approaches to reprogram the immunosuppressive tumor microenvironment. Here, we performed flow cytometry and single-cell RNA sequencing (scRNA-seq) of patient LUAD samples to comprehensively characterize LUAD-infiltrating mast cells. Mast cells exhibited functional heterogeneity and were enriched in LUAD with ground-glass opacity features (gLUAD). The mast cells in gLUAD exhibited proinflammatory and chemotactic properties while those in radiologically solid LUAD (sLUAD) were associated with tumor angiogenesis. Mast cells were an important source of CCL2 and correlated with the recruitment of CCR2+ CTL, a specific subcluster of preexhausted T cells with tissue-resident memory phenotype and enhanced cytotoxicity. Increased infiltration of mast cells and CCR2+ CTLs and their colocalization showed a strong association with favorable prognosis after surgery but were not associated with improved survival after chemotherapy. Collectively, these findings reveal a key role of mast cells in LUAD and their potential cross-talk with CTLs, suggesting that targeting mast cells may be an immunotherapeutic strategy for LUAD. Significance: Comprehensive characterization of mast cells in lung adenocarcinoma elucidates their heterogeneity and identifies interplay between mast cells and CCR2+ T cells that is associated with a favorable prognosis.
3D Prestress Bioprinting of Directed Tissues
Authors: Yuanrong Li, Jianguo Wu, Chuanjiang He, Honghui He, Mingjun Xie, Ke Yao, Jing He, Yan Duan, Liujing Zhaung, Ping Wang, Yong He
Journal: Advanced Healthcare Materials (2023)

Many mammalian tissues adopt a specific cellular arrangement under stress stimulus that enables their unique function. However, conventional 3D encapsulation often fails to recapitulate the complexities of these arrangements, thus motivating the need for advanced cellular arrangement approaches. Here, an original 3D prestress bioprinting approach of directed tissues under the synergistic effect of static sustained tensile stress and molecular chain orientation, with an aid of slow crosslinking in bioink, is developed. The semi-crosslinking state of the designed bioink exhibits excellent elasticity for applying stress on the cells during the sewing-like process. After bioprinting, the bioink gradually forms complete crosslinking and keeps the applied stress force to induce cell-orientated growth. More importantly, multiple cell types can be arranged directionally by this approach, while the internal stress of the hydrogel filament is also adjustable. In addition, compared with conventional bioprinted skin, the 3D prestress bioprinted skin results in a better wound healing effect due to promoting the angiogenesis of granulation tissue. This study provides a prospective strategy to engineer skeletal muscles, as well as tendons, ligaments, vascular networks, or combinations thereof in the future.
The DRD2 Antagonist Haloperidol Mediates Autophagy-Induced Ferroptosis to Increase Temozolomide Sensitivity by Promoting Endoplasmic Reticulum Stress in Glioblastoma
Authors: Linyong Shi, Hanning Chen, Kunxiang Chen, Chengzong Zhong, Chong Song, Yifeng Huang, Tong Wang, Lei Chen, Chiyang Li, Annie Huang, Songtao Qi, Hong Li, Yuntao Lu
Journal: Clinical Cancer Research (2023)

Temozolomide resistance remains a major obstacle in the treatment of glioblastoma (GBM). The combination of temozolomide with another agent could offer an improved treatment option if it could overcome chemoresistance and prevent side effects. Here, we determined the critical drug that cause ferroptosis in GBM cells and elucidated the possible mechanism by which drug combination overcomes chemoresistance.Haloperidol/temozolomide synergism was assessed in GBM cell lines with different dopamine D2 receptor (DRD2) expression in vitro and in vivo. Inhibitors of ferroptosis, autophagy, endoplasmic reticulum (ER) stress and cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) were used to validate the specific mechanisms by which haloperidol and temozolomide induce ferroptosis in GBM cells.In the present work, we demonstrate that the DRD2 level is increased by temozolomide in a time-dependent manner and is inversely correlated with temozolomide sensitivity in GBM. The DRD2 antagonist haloperidol, a butylbenzene antipsychotic, markedly induces ferroptosis and effectively enhances temozolomide efficacy in vivo and in vitro. Mechanistically, haloperidol suppressed the effect of temozolomide on cAMP by antagonizing DRD2 receptor activity, and the increases in cAMP/PKA triggered ER stress, which led to autophagy and ferroptosis. Furthermore, elevated autophagy mediates downregulation of FTH1 expression at the posttranslational level in an autophagy-dependent manner and ultimately leads to ferroptosis.Our results provide experimental evidence for repurposing haloperidol as an effective adjunct therapy to inhibit adaptive temozolomide resistance to enhance the efficacy of chemoradiotherapy in GBM, a strategy that may have broad prospects for clinical application.
Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke
Authors: Steven J. Warach, Anna Ranta, Joosup Kim, Shlee S. Song, Adam Wallace, James Beharry, Daniel Gibson, Dominique A. Cadilhac, Christopher F. Bladin, Timothy J. Kleinig, Jackson Harvey, Logesh Palanikumar, Vinodh T. Doss, Ruth Marescalco, John N. Fink, Alicia Tyson, Konrad H. Schlick, Lydia Noh, Duncan Wilson, Sonia Figueroa, Marco A. Pech, Laurie B. Paletz, Maya K. Lewis, Marissa Castro, Daniel H. Sahlein, E. Frank Lafranchise, Justin Sandall, Kaiz S. Asif, Scott R. Geraghty, Paul A. Cullis, Tim Malisch, Terry A. Neill, Marian P. LaMonte, Bruce C. V. Campbell, Teddy Y. Wu
Journal: JAMA Neurology (2023)

Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy. Many stroke centers have adopted 0.25-mg/kg tenecteplase instead of alteplase for stroke thrombolysis based on evidence from randomized comparisons to alteplase as well as for its practical advantages. There have been no significant differences in symptomatic intracranial hemorrhage (sICH) reported from randomized clinical trials or published case series for the 0.25-mg/Kg dose.
Self-oxygenation of engineered living tissues orchestrates osteogenic commitment of mesenchymal stem cells
Authors: Shabir Hassan, Ting Wang, Kun Shi, Yike Huang, Maria Elizabeth Urbina Lopez, Kaifeng Gan, Mo Chen, Niels Willemen, Haroon Kalam, Eder Luna-Ceron, Berivan Cecen, Gihan Daw Elbait, Jinghang Li, Luis Enrique Garcia-Rivera, Melvin Gurian, Mudassir Meraj Banday, Kisuk Yang, Myung Chul Lee, Weida Zhuang, Castro Johnbosco, Oju Jeon, Eben Alsberg, Jeroen Leijten, Su Ryon Shin
Journal: Biomaterials (2023)
Return to play following injury: whose decision should it be?
Authors: Ian Shrier, Parissa Safai, Lyn Charland
Journal: British Journal of Sports Medicine (2013)

Background Return-to-play (RTP) decision-making is required for every injured athlete. However, these decisions often lead to conflict between sport medicine professionals, athletes, coaches and sport associations. This study explores differences in professionals’ opinion about which criteria should be used for RTP decisions, and who is best able to evaluate them. Methods We surveyed Canadian sport medicine physicians, physiotherapists, athletic therapists, chiropractors, massage therapists, athletes, coaches and representatives from three sport associations. The 10 min online survey asked respondents to rate criteria as mandatory to irrelevant on a five-point Likert scale, and to indicate which profession was best able to evaluate the criteria. Results In general, medical doctors, physiotherapists and athletic therapists were considered best able to assess factors related to risk of injury and complications from injury. Each clinician group (except sport massage therapists) generally believed their own profession has the best capacity to evaluate the criteria. Athletes, coaches and sport associations were considered to have the best capacity to assess factors related to competition (desire, psychological and financial impact and loss of competitive standing). There remained considerable heterogeneity both between and within stakeholder groups. Conclusions We found that differences in approach to RTP decisions were generally greater within versus between-stakeholder groups. If shared decision-making is to become the norm in clinical sport medicine, we need to begin a discussion on which discrepancies are due to lack of training (resolved through education) or scientific knowledge (resolved through research) or simply reflect the divergence of personal/societal values.
Linguistically mediated tool use and exchange by chimpanzees (<i>Pan troglodytes</i>)
Authors: E. Sue Savage-Rumbaugh, Duane M. Rumbaugh, Sally Boysen
Journal: Behavioral and Brain Sciences (1978)

Abstract Two chimpanzees have demonstrated the ability to learn to use graphic symbols to ask one another for tools needed to obtain food. The chimps readily attended to and complied with one another's requests by selecting the appropriate tool from six distinct alternatives. They then shared the food obtained by this means and readily reversed the roles of tool requester and tool provider. Their joint accuracy was 92%, even when human experimenters were absent from the room. When they were prevented from using the graphic system (by deactivation of their keyboards), joint accuracy dropped to 10%, even though the animals could still see and hear one another and could gesture or vocalize freely. The acquisition of tool names revealed that words are at first closely and concretely linked to function, and hence that the traditional object-naming paradigm alone is a comparatively difficult starting point for the chimpanzee. This work has demonstrated that two chimpanzees have been able to comprehend the symbolic and communicative function of the symbols they use. The results raise questions concerning chimpanzee research employing other kinds of symbolic communication systems. Apparently there is little evidence, apart from anecdote or uncontrolled tests, demonstrating that either Washoe or Sarah (chimps in other investigator's projects) has fully comprehended the symbolic nature and the communicative potential of their respective gestural and graphic token symbol systems.
Supraventricular Tachycardia
Authors: Leonard I. Ganz, Peter L. Friedman
Journal: New England Journal of Medicine (1995)

Supraventricular tachycardia is any tachyarrhythmia that requires atrial or atrioventricular junctional tissue for its initiation and maintenance. Decades ago the term "paroxysmal atrial tachycardia" was coined to describe supraventricular tachycardia that began and ended abruptly. This term has become obsolete, however, since it is now clear that many such arrhythmias arise in the atrioventricular junction, not in atrial muscle itself. Much of our present knowledge about the sites of origin and mechanisms of supraventricular tachycardia has been derived from cellular electrophysiologic studies and from clinical electrophysiologic studies using the technique of programmed electrical stimulation.1,2 We have learned that such . . .
Association Between Mobilization and Composite Postoperative Complications Following Major Elective Surgery
Authors: Alparslan Turan, Ashish K. Khanna, Jack Brooker, Amit K. Saha, Clancy J. Clark, Anusha Samant, Elif Ozcimen, Xuan Pu, Kurt Ruetzler, Daniel I. Sessler
Journal: JAMA Surgery (2023)

Importance Mobilization after surgery is a key component of Enhanced Recovery after Surgery (ERAS) pathways. Objective To evaluate the association between mobilization and a collapsed composite of postoperative complications in patients recovering from major elective surgery as well as hospital length of stay, cumulative pain scores, and 30-day readmission rates. Design, Setting, and Participants This retrospective observational study conducted at a single quaternary US referral center included patients who had elective surgery between February 2017 and October 2020. Mobilization was assessed over the first 48 postoperative hours with wearable accelerometers, and outcomes were assessed throughout hospitalization. Patients who had elective surgery lasting at least 2 hours followed by at least 48 hours of hospitalization were included. A minimum of 12 hours of continuous accelerometer monitoring was required without missing confounding variables or key data. Among 16 203 potential participants, 8653 who met inclusion criteria were included in the final analysis. Data were analyzed from February 2017 to October 2020. Exposures Amount of mobilization per hour for 48 postoperative hours. Outcomes The primary outcome was a composite of myocardial injury, ileus, stroke, venous thromboembolism, pulmonary complications, and all-cause in-hospital mortality. Secondary outcomes included hospital length of stay, cumulative pain scores, and 30-day readmission. Results Of 8653 included patients (mean [SD] age, 57.6 [16.0] years; 4535 [52.4%] female), 633 (7.3%) experienced the primary outcome. Mobilization time was a median (IQR) of 3.9 (1.7-7.8) minutes per monitored hour overall, 3.2 (0.9-7.4) in patients who experienced the primary outcome, and 4.1 (1.8-7.9) in those who did not. There was a significant association between postoperative mobilization and the composite outcome (hazard ratio [HR], 0.75; 95% CI, 0.67-0.84; P &amp;amp;lt; .001) for each 4-minute increase in mobilization. Mobilization was associated with an estimated median reduction in the duration of hospitalization by 0.12 days (95% CI, 0.09-0.15; P &amp;amp;lt; .001) for each 4-minute increase in mobilization. The were no associations between mobilization and pain score or 30-day readmission. Conclusions and Relevance In this study, mobilization measured by wearable accelerometers was associated with fewer postoperative complications and shorter hospital length of stay.
Concerns About Data in Study Reporting an Association Between Abortion Restrictions and Suicide—Reply
Authors: Jonathan Zandberg, Rebecca Waller, Ran Barzilay
Journal: JAMA Psychiatry (2023)

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Relative impact of traditional vs. newer oral antifungals for dermatophyte toenail onychomycosis: a network meta-analysis study
Authors: Aditya K Gupta, Maanasa Venkataraman, Mary A Bamimore
Journal: British Journal of Dermatology (2023)

Abstract Background There is a paucity of evidence regarding the relative therapeutic efficacy of treatments for onychomycosis. Objectives We determined the relative efficacy of monotherapies for dermatophyte toenail onychomycosis with Bayesian network meta-analyses (NMAs). Methods We searched PubMed, Scopus, EMBASE (Ovid) and CINAHL to identify studies that investigated the efficacy of monotherapy with oral antifungals for dermatophyte toenail onychomycosis in adults. In this paper, ‘regimen’ corresponds to a given agent and its dosage. The relative effects and surface under the cumulative ranking curve (SUCRA) values of the various regimens were estimated; evidence quality was assessed at the study level and across networks. Results Data from 21 studies were used. Our two efficacy-related endpoints were: (i) mycological and (ii) complete cure at 1 year; safety-­related endpoints were: (i) 1-year count of any adverse event (AE), (ii) 1-year odds of discontinuation due to any AE, (iii) 1-year odds of discontinuation due to liver issues. Thirty-five regimens were identified; the newer agents among these included posaconazole and oteseconazole. We compared the efficacy of newer regimens with traditional ones like ‘terbinafine 250 mg daily for 12 weeks’ and ‘itraconazole 200 mg daily for 12 weeks. We found that an agent’s dosage was associated with its efficacy; for example, the 1-year odds of mycological cure with terbinafine 250 mg daily for 24 weeks (SUCRA = 92.4%) were significantly greater than those of terbinafine 250 mg daily for 12 weeks (SUCRA = 66.3%) (odds ratio 2.62, 95% credible interval 1.57–4.54). We also found that booster regimens can increase efficacy. Our results showed that some triazoles could be more effective than terbinafine. Conclusions This is the first NMA study of monotherapeutic antifungals – and their various dosages – for dermatophyte toenail onychomycosis. Our findings could provide guidance for the selection of the most appropriate antifungal agent, especially amid the growing concerns about terbinafine resistance.
Allostatic Load and Endocrine Disorders
Authors: Nicoletta Sonino, Giovanni A Fava, Marcella Lucente, Jenny Guidi
Journal: Psychotherapy and Psychosomatics (2023)

The building of life stress, well expressed by the concept of allostatic load, plays an important part in all phases of endocrine illness. Allostatic load refers to the cumulative burden of both stressful life events and chronic stress. When environmental challenges exceed the individual ability to cope, allostatic overload ensues. Assessment of allostatic load/overload by clinical measurements including indices and rating scales, in addition to biomarkers, offers a characterization of the person’s psychosocial environment that is missing from current formulations. Consideration of allostatic load in endocrinology may shed light on a number of clinical issues: interpretation of abnormal hormone values that lack explanations; coping with the various phases of illness; maladaptive illness behavior; response to treatment; presence of residual symptoms; health-damaging lifestyle habits. Addressing allostatic load calls for innovative models of endocrine outpatients with multidisciplinary organization of care, extended time for the interview, focus on rehabilitation. We provide an overview on the mechanisms of allostatic load, how it can be assessed, its potential role in endocrine disturbances, and how its consideration may lead to a needed innovation in patient care.